Study Escalating Doses of PM01183 in Combination With Fixed Doxorubicin in Patients With Specific Advanced Unresectable Solid Tumors | RxWiki

Study Escalating Doses of PM01183 in Combination With Fixed Doxorubicin in Patients With Specific Advanced Unresectable Solid Tumors

Overview[ - collapse ][ - ]

Purpose	Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination with Fixed Doxorubicin in Non- Heavily Pretreated Patients with Selected Advanced Solid Tumors to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with doxorubicin, to characterize the safety profile and feasibility of this combination, to characterize the pharmacokinetics (PK) of this combination, to obtain preliminary information on the clinical antitumor activity and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed to PM01183 and doxorubicin at the RD in order to assess potential markers of response and/or resistance.
Condition	Endometrial Adenocarcinomas Neuroendocrine Tumors Small-cell Lung Cancer With Less Than 2 Prior Cytotoxic-containing Lines of Therapy)
Intervention	Drug: lurbinectedin (PM01183) Drug: Doxorubicin
Phase	Phase 1
Sponsor	PharmaMar
Responsible Party	PharmaMar
ClinicalTrials.gov Identifier	NCT01970540
First Received	October 22, 2013
Last Updated	October 28, 2013
Last verified	October 2013

Tracking Information[ + expand ][ + ]

First Received Date	October 22, 2013
Last Updated Date	October 28, 2013
Start Date	June 2011
Estimated Primary Completion Date	June 2014
Current Primary Outcome Measures	Recommended Dose (RD) [Time Frame: 18 months] [Designated as safety issue: Yes]The RD will be the highest dose level explored in which less than one third of evaluable patients experience a Dose Limiting Toxicity (DLT) during Cycle 1.
Current Secondary Outcome Measures	Pharmacokinetics (PK) characterisation [Time Frame: 18 months] [Designated as safety issue: No]The dose-exposure relationships for maximum plasma concentration (Cmax) and area under the curve (AUC) will be evaluated. Pharmacogenomic (PGx) analysis [Time Frame: 18 months] [Designated as safety issue: No]Pharmacogenomics will be evaluated in order to determine predictive/prognostic markers of response and/or resistance to PM01183 and doxorubicin. Preliminary antitumor efficacy [Time Frame: 42 months] [Designated as safety issue: No]Recommended Dose expansion is ongoing in selected tumor types in order to confirm preliminary evidence of activity, specifically the study is recruiting patients with neuroendocrine tumors (NETs), or endometrial adenocarcinomas or SCLC (with less than 2 systemic chemotherapy-containing prior lines of therapy)

Descriptive Information[ + expand ][ + ]

Brief Title	Study Escalating Doses of PM01183 in Combination With Fixed Doxorubicin in Patients With Specific Advanced Unresectable Solid Tumors
Official Title	Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Doxorubicin in Non-heavily Pretreated Patients With Selected Advanced Solid Tumors
Brief Summary	Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination with Fixed Doxorubicin in Non- Heavily Pretreated Patients with Selected Advanced Solid Tumors to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with doxorubicin, to characterize the safety profile and feasibility of this combination, to characterize the pharmacokinetics (PK) of this combination, to obtain preliminary information on the clinical antitumor activity and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed to PM01183 and doxorubicin at the RD in order to assess potential markers of response and/or resistance.
Detailed Description	The study has currently met its primary end point and is now recruiting patients to be treated at the RD expansion cohort of selected tumor types, specifically: endometrial adenocarcinomas, neuroendocrine tumors, and small-cell lung cancer (SCLC).
Study Type	Interventional
Study Phase	Phase 1
Study Design	Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Endometrial Adenocarcinomas Neuroendocrine Tumors Small-cell Lung Cancer With Less Than 2 Prior Cytotoxic-containing Lines of Therapy)
Intervention	Drug: lurbinectedin (PM01183) lurbinectedin (PM01183) is presented as powder for concentrate for solution for infusion with two strengths, 1-mg and 4-mg vials. Drug: Doxorubicin Doxorubicin 50 mg injectable solution
Study Arm (s)	Experimental: lurbinectedin (PM01183) / doxorubicin Doxorubicin 50 mg/m2 administered as an intravenous (i.v.) bolus followed by PM01183 4.0 mg flat dose (FD) as a 1-hour i.v. infusion on Day 1 every 3 weeks

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	73
Estimated Completion Date	June 2014
Estimated Primary Completion Date	June 2014
Eligibility Criteria	Inclusion Criteria: - Voluntarily written informed consent - Age: between 18 and 75 years (both inclusive). - Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. - Life expectancy ≥ 3 months. - Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors: 1. Breast cancer 2. Soft-tissue sarcoma 3. Primary bone sarcomas. 4. Gynecologic tumors (endometrial adenocarcinomas, epithelial ovarian cancer...) 5. Hepatocellular carcinoma 6. Gastroenteropancreatic neuroendocrine tumors 7. Small cell lung cancer (SCLC) 8. Gastric cancer 9. Bladder cancer 10. Adenocarcinoma of unknown primary site - At least three weeks since the last anticancer therapy, including radiotherapy - Adequate bone marrow, renal, hepatic, and metabolic function - Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional standards). - Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment Exclusion Criteria: - Concomitant diseases/conditions: - History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year. - Symptomatic or any uncontrolled arrhythmia - Ongoing chronic alcohol consumption, or cirrhosis - Active uncontrolled infection. - Known human immunodeficiency virus (HIV) infection. - Any other major illness that, in the Investigator's judgment - Brain metastases or leptomeningeal disease involvement. - Men or women of childbearing potential who are not using an effective method of contraception - Patients who have had radiation therapy in more than 35% of the bone marrow. - History of previous bone marrow and/or stem cell transplantation.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Spain, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number	NCT01970540
Other Study ID Numbers	PM1183-A-003-10
Has Data Monitoring Committee	No
Information Provided By	PharmaMar
Study Sponsor	PharmaMar
Collaborators	Not Provided
Investigators	Study Chair: Sergio Szyldergemajn, MD Pharma Mar
Verification Date	October 2013

Locations[ + expand ][ + ]

Hospital Universitario Madrid Sanchinarro	Madrid, Spain Contact: Emiliano Calvo, MD \| 91 756 78 00 \| emiliano.calvo@start.stoh.com Principal Investigator: Emiliano Calvo, MD Recruiting
UCLH (University College London Hospitals)	London, United Kingdom Contact: Martin Forster, MD \| +44 0845 155 5000 \| martin.foster@cancer.ucl.ac.uk Principal Investigator: Martin Forster, MD Recruiting